期刊
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
卷 23, 期 9, 页码 -出版社
MDPI
DOI: 10.3390/ijms23094629
关键词
hepatitis B virus; affinity; MM-GBSA; residue scanning; molecular dynamics
资金
- National Natural Science Foundation of China [31871322]
- Space Medical Experiment Project of China Manned Space Program [6931008127]
- Fundamental Research Funds for the Central Universities [2242017K3DN23, 2242017K41041]
- Jiangsu Provincial Science and Technology Fund of China [BE2017714]
This study proposes a novel prediction strategy based on structure to assess the affinity between HBV antigenic peptides and HLA molecules. Through residue scanning, peptide docking, and molecular dynamics methods, the researchers obtained the molecular docking model of HBV peptide and HLA, and calculated the binding affinity using the MM-GBSA method. The results were consistent with experimental assays, indicating the accuracy of the affinity prediction process and the reliability of the HLA homologous modeling strategy.
Chronic hepatitis B virus (HBV), a potentially life-threatening liver disease, makes people vulnerable to serious diseases such as cancer. T lymphocytes play a crucial role in clearing HBV virus, while the pathway depends on the strong binding of T cell epitope peptide and HLA. However, the experimental identification of HLA-restricted HBV antigenic peptides is extremely time-consuming. In this study, we provide a novel prediction strategy based on structure to assess the affinity between the HBV antigenic peptide and HLA molecule. We used residue scanning, peptide docking and molecular dynamics methods to obtain the molecular docking model of HBV peptide and HLA, and then adopted the MM-GBSA method to calculate the binding affinity of the HBV peptide-HLA complex. Overall, we collected 59 structures of HLA-A from Protein Data Bank, and finally obtained 352 numerical affinity results to figure out the optimal bind choice between the HLA-A molecules and 45 HBV T cell epitope peptides. The results were highly consistent with the qualitative affinity level determined by the competitive peptide binding assay, which confirmed that our affinity prediction process based on an HLA structure is accurate and also proved that the homologous modeling strategy for HLA-A molecules in this study was reliable. Hence, our work highlights an effective way by which to predict and screen for HLA-peptide binding that would improve the treatment of HBV infection.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据